{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T15:19:05Z","timestamp":1789917545937,"version":"4.0.1"},"reference-count":48,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T00:00:00Z","timestamp":1570752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["HI16C2044"],"award-info":[{"award-number":["HI16C2044"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003621","name":"Ministry of Science, ICT and Future Planning","doi-asserted-by":"publisher","award":["2018R1A5A2025286 and 2017R1C1B3002626"],"award-info":[{"award-number":["2018R1A5A2025286 and 2017R1C1B3002626"]}],"id":[{"id":"10.13039\/501100003621","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Antiplatelet agents are important in the pharmacotherapeutic regime for many cardiovascular diseases, including thrombotic disorders. However, bleeding, the most serious adverse effect associated with current antiplatelet therapy, has led to many efforts to discover novel anti-platelet drugs without bleeding issues. Of note, shear stress-induced platelet aggregation (SIPA) is a promising target to overcome bleeding since SIPA happens only in pathological conditions. Accordingly, this study was carried out to discover antiplatelet agents selectively targeting SIPA. By screening various herbal extracts, Paeonia suffruticosa and its major bioactive constituent, paeoniflorin, were identified to have significant inhibitory effects against shear-induced aggregation in human platelets. The effects of paeoniflorin on intraplatelet calcium levels, platelet degranulation, and integrin activation in high shear stress conditions were evaluated by a range of in vitro experiments using human platelets. The inhibitory effect of paeoniflorin was determined to be highly selective against SIPA, through modulating von Willebrand Factor (vWF)-platelet glycoprotein Ib (GP Ib) interaction. The effects of paeoniflorin on platelet functions under high shear stress were confirmed in the ex vivo SIPA models in rats, showing the good accordance with the anti-SIPA effects on human platelets. Treatment with paeoniflorin significantly prevented arterial thrombosis in vivo from the dose of 10 mg\/kg without prolonging bleeding time or blood clotting time in rats. Collectively, our results demonstrated that paeoniflorin can be a novel anti-platelet agent selectively targeting SIPA with an improved safety profile.<\/jats:p>","DOI":"10.3390\/ijms20205040","type":"journal-article","created":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T10:53:03Z","timestamp":1570791183000},"page":"5040","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Antithrombotic Effects of Paeoniflorin from Paeonia suffruticosa by Selective Inhibition on Shear Stress-Induced Platelet Aggregation"],"prefix":"10.3390","volume":"20","author":[{"given":"Thien","family":"Ngo","sequence":"first","affiliation":[{"name":"College of Pharmacy, Seoul National University, Seoul 08826, Korea"},{"name":"Faculty of Pharmacy, Thai Binh University of Medicine and Pharmacy, Thai Binh city 410000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keunyoung","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiying","family":"Bian","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Seoul National University, Seoul 08826, Korea"},{"name":"School of Public Health, China Medical University, Shenyang 110122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hakjun","family":"Noh","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-Min","family":"Lim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Ewha Womans University, Seoul 03760, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Ho","family":"Chung","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0583-2116","authenticated-orcid":false,"given":"Ok-Nam","family":"Bae","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Hanyang University, Ansan 15588, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1161\/CIR.0000000000000366","article-title":"American Heart Association Statistics, C.; Stroke Statistics, S., Executive Summary: Heart Disease and Stroke Statistics--2016 Update: A Report From the American Heart Association","volume":"133","author":"Mozaffarian","year":"2016","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/nrcardio.2017.206","article-title":"Current and future antiplatelet therapies: Emphasis on preserving haemostasis","volume":"15","author":"McFadyen","year":"2018","journal-title":"Nat. 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